Adhesive biopolymers and uses thereof

Patent metadata

Field	Value
Publication number	US-9687583-B2
Application number	US-201214342392-A
Country	US
Kind code	B2
Filing date	Aug 30, 2012
Priority date	Sep 1, 2011
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

Provided herein are polymers having the general formula I as defined herein,

A-L-B  Formula I

as well as crosslinked polymers having the general formula III:

B′-L′-A′-A″-L″-B″  Formula III

and methods of preparing the polymers, wherein A is a dihydroxyphenyl moiety; A′-A″ is a pair of crosslinked dihydroxyphenyl moieties; B, B′ and B″ are each a biopolymer; and L, L′ and L″ are each a linking moiety. Further provided are crosslinked adhesives prepared from the polymers, methods of generating same by oxidizing a polymer, and uses thereof. Further provided are kits comprising an adhesive and an oxidizing agent.

First claim

What is claimed is:

1. A polymer having the general formula I:
A-L-B  Formula I

wherein:
B is a biopolymer which is a polypeptide comprising at least one resilin amino acid sequence;
L is a linking moiety; and
A is a dihydroxyphenyl moiety having the general formula II:

wherein each of R 1 -R 5 is independently selected from the group consisting of hydrogen and hydroxyl, and at least two of R 1 -R 5 are hydroxyl.

2. The polymer of claim 1 , wherein at least one of R 1 -R 5 is hydrogen.

3. The polymer of claim 1 , wherein at least 90% of the total amount of dihydroxyphenyl moieties of the polymer are not crosslinked.

4. The polymer of claim 1 , wherein said dihydroxyphenyl moiety and said linking moiety form a part of a DOPA residue.

5. The polymer of claim 1 , wherein said dihydroxyphenyl moiety and said linking moiety do not form a part of a DOPA residue.

6. The polymer of claim 1 , comprising a plurality of said dihydroxyphenyl moiety.

7. The polymer of claim 6 , wherein a ratio of molecular weight of the polymer to dihydroxyphenyl moieties comprised by the polymer is in a range of from 1.5 KDa per dihydroxyphenyl moiety to 12 KDa per dihydroxyphenyl moiety.

8. The polymer of claim 6 , being a polypeptide wherein a percentage of amino acid residues of said polypeptide which comprise said dihydroxyphenyl moiety is in a range of from 0.5% to 5%.

9. The polymer of claim 1 , exhibiting an adhesiveness to a surface, said adhesiveness comprising resistance to stress of 1 KPa in a direction perpendicular to said surface.

10. A method of preparing the polymer of claim 5 , wherein said linking moiety is attached to said biopolymer via a covalent bond formed between a reactive group in said linking moiety and a functional group on said biopolymer, the method comprising:
a) providing a compound comprising said dihydroxyphenyl moiety and said reactive group; and
b) contacting said compound with a biopolymer comprising at least one of said functional group, said biopolymer comprising at least one resilin amino acid sequence, to form said covalent bond,
thereby preparing the polymer.

11. A method of preparing the polymer of claim 1 , the method comprising:
a) providing a biopolymer comprising at least one hydroxyphenyl moiety, said biopolymer comprising at least one resilin amino acid sequence; and
b) oxidizing at least one of said at least one hydroxyphenyl moiety to form said dihydroxyphenyl moiety,
thereby preparing the polymer.

12. The method of claim 11 , wherein said oxidizing is effected by contacting said biopolymer with a tyrosine hydroxylase.

13. The method of claim 11 , wherein at least 90% of the total amount of dihydroxyphenyl moieties of said polymer are not crosslinked.

14. The method of claim 11 , wherein said oxidizing is effected by a Fenton reaction.

15. A method of generating a crosslinked adhesive, the method comprising contacting the polymer of claim 1 with an oxidizing agent, to thereby crosslink said dihydroxyphenyl moieties of said polymer.

16. A method of binding a first agent to a second agent, the method comprising contacting the first agent with said second agent in a presence of the polymer of claim 1 and an oxidizing agent.

17. The method of claim 15 , wherein said contacting is effected in vivo.

18. A kit comprising:
a) an adhesive comprising the polymer of claim 1 ; and
b) an oxidizing agent.

19. A crosslinked polymer having the general formula III:
B′-L′-A′-A″-L″-B″  Formula III

wherein:
B′ and B″ are each independently a biopolymer which is a polypeptide comprising at least one resilin amino acid sequence;
L′ and L″ are each a linking moiety; and
A′-A″ is a pair of crosslinked dihydroxyphenyl moieties, said pair having a formula selected from the group consisting of:

wherein each of R′ 1 -R′ 5 and R″ 1 -R″ 5 is independently selected from the group consisting of hydrogen and hydroxy, and at least two of R′ 1 -R′ 5 and at least two of R″ 1 -R″ 5 are hydroxy,
with the proviso that said biopolymer is not blended with a polysaccharide.

20. The crosslinked polymer of claim 19 , comprising a plurality of said pair of crosslinked dihydroxyphenyl moieties.

21. The crosslinked polymer of claim 19 , exhibiting an adhesiveness to a surface, said adhesiveness comprising resistance to shear stress of 1.5 MPa.

22. The crosslinked polymer of claim 19 , exhibiting an adhesiveness to a surface, said adhesiveness comprising resistance to stress of 10 KPa in a direction perpendicular to said surface.

Assignees

• Shoseyov Oded
• Lapidot Shaul
• Rivkin Amit
• Yissum Res Dev Co
• Collplant Ltd

Inventors

• Shoseyov Oded
• Lapidot Shaul
• Rivkin Amit

Classifications

• C08J3/24 Primary

  Crosslinking, e.g. vulcanising, of macromolecules (mechanical aspects B29C35/00; crosslinking agents C08K) · CPC title

• C08J2300/16

  Biodegradable polymers · CPC title

• A61L2430/06

  for cartilage reconstruction, e.g. meniscus · CPC title

• C08H1/00

  Macromolecular products derived from proteins (food proteins A23; glue, gelatine C09H) · CPC title

• C09J189/00

  Adhesives based on proteins; Adhesives based on derivatives thereof · CPC title